Diisopropylethylamine → (S)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(5-fluoropyridin-2-yl)ethylamino) nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,5-difluoronicotinonitrile (Method 32, 5.75 g, 22.0 mmol), in n-BuOH (28.75 ml) was prepared at room temperature in a 48 ml sealed tube. DIEA (4.98 ml, 28.6 mmol) was then added, followed by the addition of (S)-1-(5-fluoropyridin-2-yl)ethanamine (Method 33; 4.0 g, 28.6 mmol). The tube was then sealed, and the suspension was heated to 130° C. over 45 minutes. The reaction was then allowed to stir at 130° C. for 18 hours. The reaction was then cooled to room temperature and concentrated by rotary evaporation at 60° C. to remove n-BuOH. The remaining oil was then taken up in DCM (100 ml) and washed with water (2×100 ml). The combined aqueous fractions were then extracted with DCM (100 ml), and the combined organic fractions were dried over Na2SO4, filtered and concentrated. The resulting oil was then purified by column chromatography (DCM, then DCM-MeOH=100:1) to give the title compound (5.2 g, 62%). 1H NMR (400 MHz, CD3OD) δ 8.43 (d, J=2.5 Hz, 1H), 7.60-7.34 (m, 3H), 6.09-5.63 (m, 1H), 5.24 (q, J=7.0 Hz, 1H), 1.91 (septet, 1H), 1.58 (d, J=6.6 Hz, 3H), 1.08-0.90 (m, 2H), 0.79-0.70 (m, 2H). MS: Calcd.: 381. Found: [M+H]+ 382.

Provenance & Evidence